Researchers Look at Genomes of Nonsmokers With Lung Cancer

MONDAY, Jan. 9 -- Scientists who have started to identify genes and pathways associated with lung cancer in people who have never smoked say it's a first step in the potential development of new treatments.

Never-smokers -- people who've smoked fewer than 100 cigarettes over a lifetime -- account for about 10 percent of lung cancer cases.

But this group of lung cancer patients hasn't been studied as much as smokers who develop lung cancer, according to Timothy Whitsett, a senior postdoctoral fellow in the cancer and cell biology division at the Translational Genomics Research Institute in Phoenix.

He and his colleagues conducted genetic analyses on three female patients with adenocarcinoma of the lung, a form of non-small cell lung cancer. One was a never-smoker with early-stage disease, one was a never-smoker with late-stage disease and one was a smoker with early-stage disease.

"In the never-smoker with early-stage cancer, there were very few mutations in the genome, but when we looked at the whole transcriptome, we saw differences in gene expression," Whitsett said in a news release from the American Association for Cancer Research.

The never-smoker with late-stage disease had mutations in what Whitsett called "classic tumor-suppressor genes." It's possible that mutations of the tumor-suppressor genes may be a factor in late-stage lung cancer in never-smokers, the researchers said.

The tumors in both never-smokers lacked alterations in common genes associated with lung cancer, such as EGFR, KRAS and EML/ALK translocations. This suggests that these patients are ideal cases for the discovery of new mutations associated with lung adenocarcinomas in never-smokers, according to Whitsett and colleagues.

The study was slated for presentation Monday at an AACR/International Association for the Study of Lung Cancer joint conference on lung cancer, held in San Diego.

"This is the starting point. We certainly have a lot of pathways and gene expression alterations that we're going to be very interested in confirming and looking at in larger cohorts of patients," Whitsett said.

He and his colleagues are now validating these findings in a larger group of never-smokers and smokers with lung adenocarcinoma.

Because the current study was presented at a medical meeting, the data and conclusions should be viewed as preliminary until published in a peer-reviewed journal.